| Abstract|| |
The conducted study aimed to determine the incidence and clinical profile of acute kidney injury (AKI) in hospitalized patients using the AKI Network (AKIN) criteria. This prospective observational study was conducted at the Pediatric ward and pediatric Intensive Care Unit of a tertiary level teaching hospital in North India. The participants were 763 consecutive patients aged three months to 12 years from January 2014 to October 2015 and were assessed for eligibility. Of these, 163 patients were excluded from the study. Main outcome measure was incidence of AKI based on the AKIN criteria. Factors associated with AKI were analyzed. A total of 600 patients (141 critically ill and 459 noncritically ill) were enrolled. The incidence of AKI was 25.2% (n = 151); it was significantly higher among critically ill (53.2%) than non-critically ill patients (16.6%), P <0.001. Most patients with AKI were in Stage 1 (n = 99; 65.6%). Ten patients (6.6%) required dialysis (peritoneal dialysis n = 8; hemodialysis n = 2). Patient with AKI had significantly higher median (interquartile range) PIM-2 score, 22.6 (5–61.7), longer hospital stay (10 vs. 7 days), and mortality rate (28.5% vs. 3.6%); P <0.001. Nephrotoxic drugs [hazard ratio (HR): 5.5, 95% confidence interval (CI): 2.6–11.4; P = 0.001]; hypovolemia (HR: 1.7, 95% CI: 1–2.7; P = 0.035); sepsis (HR 2.3, 95% CI: 1.1–5); and mechanical ventilation (HR: 3.3, 95% CI: 1.6–6.8) were independent predictors for AKI. AKI was an independent risk factor for mortality and risk increased with increasing stage of AKI. Mortality was significantly higher in Stage 3 AKI (n = 14; 60.9%); P <0.001. Independent predictors for mortality in AKI were acidosis (HR: 3.6; 95% CI 1.5–8.6), mechanical ventilation (HR: 34; 95% CI 9.3-123), shock (HR: 19.7; 95% CI 2–194), and sepsis (HR: 3; 95% CI 1-8). The incidence of AKI is high among pediatric patients admitted to this center, including among noncritically ill children. AKI is associated with significantly increased morbidity and mortality.
|How to cite this article:|
Nawaz S, Afzal K. Pediatric acute kidney injury in North India: A prospective hospital-based study. Saudi J Kidney Dis Transpl 2018;29:689-97
|How to cite this URL:|
Nawaz S, Afzal K. Pediatric acute kidney injury in North India: A prospective hospital-based study. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Jun 18];29:689-97. Available from: http://www.sjkdt.org/text.asp?2018/29/3/689/235172
| Introduction|| |
Acute kidney injury (AKI), formerly known as acute renal failure (ARF), is a common problem in hospitalized pediatric patients, associated with increased morbidity and mortality. To provide a uniform definition and classification to standardize patient care and compare epidemiological data across studies, the term ARF was replaced by AKI., Studies of critically ill children and adults consistently show that even a small increment in serum creatinine of 0.3 mg/dL is independently associated with survival, after demographic characteristic, comorbidities, severity of illness, and complications have been controlled for.
The etiology and management of AKI differ extensively not only between developing and developed countries, but also even within the same country, from one center to another, depending on the location, level of expertise, and resources available at the center. Furthermore, as in adults, AKI carries a significant risk for late development of chronic kidney disease (CKD) in surviving children.
Most pediatric studies on the incidence of AKI are limited to developed countries and often based on retrospective data.,,, Few prospective studies have been conducted to determine the incidence and clinico-etiological profile of AKI, in children from India in recent years.,,, Data on incidence and clinical profile of AKI will help to increase awareness of AKI among physicians, community, and above all the policymakers, which should help in designing effective strategies for early diagnosis and intervention of AKI.
The current study was undertaken to find the incidence, clinical profile, and short-term outcome of AKI as defined by AKI Network (AKIN) classification among children presenting to this hospital. Predictors of AKI and mortality were also assessed.
| Materials and Methods|| |
Aligarh is situated in the Western part of Uttar Pradesh, the most populous state of North India, nearly 90 miles southeast of the capital New Delhi. The district has a population of nearly 3.7 million; approximately one-third of these are children aged below 14 years. Jawaharlal Nehru Medical College is a referral teaching hospital that caters to Aligarh and a wide catchment area of Northwest India. This prospective observational study was conducted during the period from January 2014 to September 2015.
Consecutive patients in the age group of three months to 12 years, admitted to pediatric wards or pediatric Intensive Care Unit (PICU) were eligible for inclusion in the study. The Institutional Ethics Committee approved the study. Informed consent was obtained from the parents or the guardian before inclusion into the study.
Patients with any of the following criteria detected at initial assessment or during the course of hospital stay were excluded from the study.
- CKD Stage V (estimated glomerular filtration rate <15 mL/min/1.73m2)
- Bilirubin level >5 mg/dL
- Hospital stay of less than 48 h
- Serum creatinine not done at admission or at 24 h
Patients were classified as critically ill, if they satisfied any one or more of the following criteria
- Admitted to the PICU
- Require mechanical ventilation
- Require vasopressor support (need for dopamine and/or dobutamine at a dose >10 pg/kg/min and or adrenaline at any dose for the management of hypotension)
- Impaired level of consciousness (Glasgow coma scale <7)
- Fulminant hepatic failure
Uncontrolled or poorly controlled seizures Patient who failed to meet these criteria were considered not critically ill. The pediatric index of mortality score 2 were computed for all patients admitted to the PICU.
Serum creatinine assessment
Serum creatinine levels were estimated by modified Jaffe method using automated analyzer machine. Measurements were done at admission and repeated every 24 ±6 h for three consecutive days in all patients. Subsequently, the estimation was done every 48 ± 12 h in AKI patients. In those not critically ill, but having risk factors (feature of dehydration, congestive heart failure or shock; diuretics or nephrotoxic agents; and new-onset sepsis), serum creatinine level was determined every 48 ± 12 h, until risk factors remit or patient is discharged. Urine output was recorded for catheterized patients. AKI was diagnosed and staged based on AKIN classification.
Information regarding demographic parameters, diagnosis, comorbidities, and duration of hospital stay was recorded on a predesigned proforma. The patients were evaluated to ascertain the etiology of AKI whenever possible, its progression and need for dialysis. The treating physicians managed AKI as per the KDIGO guidelines. Standard definitions were used to identify shock, sepsis, and hypertension.
Patients were followed until discharge, and the outcome was examined in relation to the maximal stage of AKI. Outcome assessed was death or survival with complete/partial renal recovery at discharge. Complete renal recovery was defined as normal urinalysis, normal blood pressure, and normal serum creatinine for age at the time of discharge (0.2–0.4 mg/dL for infants, 0.3–0.7 mg/dL for 1–12 years, and 0.5–1 mg/dL for > 12 years). Partial renal recovery at discharge was considered in the presence of any one or more of the following: hypertension, abnormal urinalysis (proteinuria >1+ by dipstick and/or urine protein to creatinine ratio >0.2 mg/mg; >5 leukocytes or red cells per high power field) or elevated serum creatinine for age. Patients requiring maintenance dialysis were classified as dialysis dependent. Those with partial renal recovery at discharge were re-evaluated at three months.
| Statistical Analysis|| |
The reported incidence of AKI in children is approximately 5%–9% among noncritically ill, and 25%–35% in critically ill children., Assuming the actual incidence is unlikely to exceed 10% among noncritically ill children and 35% in critically ill children, a sample size of 384 and 137, respectively was calculated to estimate the true incidence rate at 95% confidence, and a precision of 3% for the non-critically ill and 8% for critically ill children.
Continuous data are presented as mean (standard deviation) if normally distributed or median [interquartile range (IQR)] for non-normally distributed data. Ordinal data were compared using Fisher's exact test or Chi-square test as appropriate. The incidence of AKI was calculated as a proportion of total patient enrolled. Relation between the stage of AKI and renal outcome at discharge was studied. Regression analysis was performed to assess factors causative of AKI as well as risk factors for mortality. Significance was taken at a P <0.05. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 21.0 for Windows (SPSS Inc., Chicago, IL, USA).
| Results|| |
A total of 763 consecutively admitted children were assessed for eligibility, of which 600 patients (141 were “critically ill” and 459 “noncritically ill”) that satisfied the inclusion criteria were enrolled into the study protocol [Figure 1]. The median (IQR) PIM-2 score in critically ill patients at admission was 27.2 (2.4–49.9). Median (IQR) age of the study population was 36 (11–84) years and 63% (n = 378) were male gender; mean duration of illness before admission was nine days for critically ill and eight days for noncritically ill patients, P = 0.370. There was no difference between critically ill and noncritically ill patients with respect to age, gender, and duration of illness before admission. Urine output was recorded only for catheterized patients (n = 106).
|Figure 1: Flow of patients in the study.|
CKD: Chronic kidney disease, AKI: Acute kidney injury.
Click here to view
A total of 151 patients developed AKI using the AKIN criteria giving an overall incidence of 25.2% among children admitted to this hospital. The incidence was significantly higher in critically ill patients [53.2% (n = 75)], as compared to noncritically patients [16.6% (n = 76)], P <0.001. Most patients were in Stage 1 AKI (n = 99; 65.6%). Ten patients (6.6%) required dialysis (peritoneal dialysis n = 8; hemodialysis n = 2). For 85 patients with AKI, serum creatinine criterion alone was satisfied, while in the remaining 66, both urine output and serum creatinine were satisfied. Among catheterized patients, 37 (56%) had nonoliguric AKI, 21 (31.8%) had oliguric AKI, and 8 (12.2%) others had anuric AKI.
In the present cohort, patients with AKI were younger, median (IQR) age of 28 (10–72) months as compared to non-AKI patients 36 (12–84) months. AKI did not correlate with any particular age group or gender in the study population. However, frequency of AKI decreased with increasing age; <1 year (n = 52; 28.9%), 1–5-year age group (n = 58; 25.9%), and >5-year age category (n = 41; 20.9%). Gender distribution was similar among AKI and non-AKI patient groups (male gender 64.2% and 62.6%, respectively, P = 0.504).
Among the critically ill patients, those that developed AKI had higher median (IQR) PIM-2 score 22.6 (5-61.7) versus patients with no AKI 5.8 (1.6-37.4), P = 0.002. Furthermore, AKI patients had significantly longer duration of hospital stay 10 (7.2) days, as compared to 7 (5) days in non-AKI patient (P <0.001). Most patients were diagnosed to have AKI at 24 h (n = 77; 51%), 48 h (n = 52; 34.4%), or at 72 h (n = 17; 11.3%) of admission; only (n = 5) 3.3% were categorized by day 7. The maximum stage of AKI was reached in most patients by 3rd day after admission (n = 100; 66.2%).
The etiology of AKI was neurological illnesses (21.2%), sepsis (19.2%), infections such as malaria (13%), respiratory illness (8%), renal diseases (8%), and acute gastroenteritis (7.2%) [Table 1].
On regression analysis, the use of nephrotoxic drugs, the presence of hypovolemia, sepsis, critical illness, and need for mechanical ventilation were independent predictors for causation of AKI [Table 2]. Drugs which were significantly associated with AKI were diuretics [hazard ratio (HR): 2.6; 95% confidence interval (CI): 1.6–4.3; P <0.001], vancomycin (HR: 3.6; 95% CI 2–6.4; P <0.001), mero-penum (HR: 3.1; 95% CI: 1.3–7.4; P = 0.008), aminoglycosides (HR: 2.6; 95% CI: 1.6–4; P <0.001), and antimalarials (HR: 2.6; 95% CI: 1.5–4.6); P = 0.001.
Mortality was significantly higher in AKI patients [43 (28.5%)], as compared to non-AKI patients [16 (3.6%)]; P <0.001. The significant risk factors of mortality on univariate analysis were shock, mechanical ventilation, critical illness, acidosis, thrombocytopenia, hypona-tremia, sepsis, anuria, total leukocyte count >15,000/μL, and AKI (P <0.001) [Table 3]. AKI was an independent risk factor for mortality (HR: 10.8, 95% CI: 5.8-19.8) and the risk increased in direct relation to increasing stage of AKI. Mortality was higher for patients in Stage 3 AKI (n = 14; 60.9%) as compared to Stage 2 (n = 12; 41.4%) and Stage 1 (n = 17; 17.2%) AKI patients, P<0.001.
The independent predictors for mortality in AKI patients were acidosis (HR: 3.6; 95% CI: 1.5–8.6; P = 0.004), mechanical ventilation (HR: 34; 95% CI 9.3–123; P <0.001), shock (HR: 19.7; 95% CI 2–194; P = 0.011), and sepsis (HR: 3; 95% CI 1–8; P = 0.038).
Among the survivors with AKI (n = 108), complete recovery of renal functions was observed in 79 (73.1%) and partial recovery in 29 (26.9%) patients. Most patients in Stage 1 AKI (n = 68; 68.7%; P <0.001) had complete renal recovery [Figure 2]. Patients with partial renal recovery were reviewed at three months, of which eight patients failed to report; of the remaining, five had persistent abnormal serum creatinine at three months and were labeled as chronic kidney disease, CKD Stage 1 (n = 3), Stage 2 (n = 1), and Stage 3 (n = 1).
| Discussion|| |
The incidence of AKI, using the AKIN criteria, was 25.2% in our study population. The incidence was three-folds higher, in critically ill patients (53.2%) compared to non-critically ill patients (16.6%). Most patients with AKI were in Stage 1 (n = 99; 65.6%). Seven percent of patients with AKI were dialyzed. Presence of AKI resulted in a longer hospital stay as compared to non-AKI patients (10 days versus 7 days; P <0.001) and eightfold higher mortality (28.5% vs. 3.6%; P <0.001), especially among critically ill and AKI Stage 2 and 3 patients. In recent prospective reports from India, the incidence of AKI has ranged from 5% to 10% in noncritically ill children,, and 15% to 36% in critically ill children.,, The incidence of AKI in our study (16.6% in noncritically ill and 53.2% in critically ill) was higher than in most other reports of AKI in children both from developed as well as developing countries,, including reports from India. The higher incidence of AKI in our study when compared to some of the other studies is possibly due to differences in resources, younger age of the study cohort, infections being the major reason for hospitalization, and frequent use of potentially nephrotoxic medications. Furthermore, about 30% of the patients categorized as critically ill could not get PICU admission due to nonavailability of beds; this may have further contributed to the higher incidence of AKI in our study.
Most patients with AKI in the study were in Stage 1 (65.6%), followed by Stage 2 (19.2%) and stage 3 (15.3%); this observation was similar to other studies., The etiology of AKI in the study was mainly neurological illness (21.2%), sepsis (19.2%), acute gastroenteritis (7.2%), infections such as malaria (13%), pneumonia, meningoencephalitis, and renal diseases as reported in other studies from the developing countries.,, Patients with sepsis, shock, mechanical ventilation, and use of nephrotoxic drug were at increased risk for AKI in our study; this observation was similar to other studies.,,, Almost 6%–45% of critically sick patients with incident AKI require renal replacement therapy,, as also confirmed by the present study wherein 7% of the AKI patients required dialysis. Complete renal recovery was observed in majority of patients with AKI who survived [n = 79 (73.1%)], similar to other studies.,,
Mortality was significantly higher in AKI patients [43 (28.5%)], as compared to non-AKI patients 16(3.6%); P <0.001. Risk for mortality was significantly higher in Stage 3 AKI patients, P <0.001. Our study confirms that AKI is an independent risk factor for mortality., Mortality figures of 28.5% among AKI patients in the present study were comparable to previous reports of 9% to 67%.,,, The mortality in this study was lower than some of the studies from India, and some developed countries.
The major strength of this study was that it was done prospectively and renal functions were checked frequently. However the study had several limitations. First, urine output was not measured in all patients; this might have resulted in under-reporting of the incidence. Second, this being a tertiary level referral hospital, patients admitted here are generally sicker, with substantial delay in seeking appropriate medical attention; therefore, incidence figures reported by us cannot be extrapolated to other settings. Third, because of higher patient load, not all critically ill patients could receive ICU care, which could have contributed to AKI and also higher mortality. Fourth, the study population had a lower median age than most other reports and young age is a known risk factor for AKI, possibly due to immature renal functions as well as higher chances of infections and volume depletion. Finally, the present study was not powered to examine predictors of mortality in AKI. Larger studies that address these risk factors are needed. Despite these limitations, it is reasonable to conclude from this study that AKI is common among hospitalized children particularly those requiring ICU admission and is an independent risk factor for mortality.
Conflict of interest: None declared.
| References|| |
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI Workgroup. Acute renal failure-definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8:R204-12.
Mehta RL, Kellum JA, Shah SV, et al. Acute kidney injury network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.
Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: A cohort analysis. Crit Care 2006;10:R73.
Mammen C, Al Abbas A, Skippen P, et al. Long-term risk of CKD in children surviving episodes of acute kidney injury in the Intensive Care Unit: A prospective cohort study. Am J Kidney Dis 2012;59:523-30.
Askenazi DJ, Ambalavanan N, Hamilton K, et al. Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and paediatric non-cardiac patients on extracorporeal membrane oxygenation. Paediatr Crit Care Med 2011;12:e1-6.
Alkandari O, Eddington KA, Hyder A, et al. Acute kidney injury is an independent risk factor for pediatric Intensive Care Unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: A two-center retrospective cohort study. Crit Care 2011;15:R146.
Gómez Polo JC, Alcaraz Romero AJ, Gil-Ruíz Gil-Esparza MA, et al. Morbimortality associated to acute kidney injury in patients admitted to pediatric Intensive Care Units. Med Intensiva 2014;38:430-7.
Joannidis M, Metnitz B, Bauer P, et al. Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. Intensive Care Med 2009;35:1692-702.
Krishnamurthy S, Narayanan P, Prabha S, et al. Clinical profile of acute kidney injury in a pediatric Intensive Care Unit from Southern India: A prospective observational study. Indian J Crit Care Med 2013;17:207-13.
] [Full text]
Mehta P, Sinha A, Sami A, et al. Incidence of acute kidney injury in hospitalized children. Indian Pediatr 2012;49:537-42.
Gullipalli P, Anjani A. Spectrum of paediatric acute kidney injury - A referral hospital experience in a developing nation. IOSR J Dent Med Sci 2015;14:80-7.
Li Philip KT, Burdmann EA, Mehta RL. Acute kidney injury: Global health alert. Acta Nephrologica 2013;27:5-10.
Schwartz GJ, Muñoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009;20:629-37.
Slater A, Shann F, Pearson G; Paediatric Index of Mortality (PIM) Study Group. PIM2: A revised version of the paediatric index of mortality. Intensive Care Med 2003;29:278-85.
Bowers LD, Wong ET. Kinetic serum creatinine assays. II. A critical evaluation and review. Clin Chem 1980;26:555-61.
Kidney Disease: Improving Global Outcome (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012;2:1-138.
Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005;6:2-8.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The Fourth Report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555-76.
Ceriotti F, Boyd JC, Klein G, et al. Reference intervals for serum creatinine concentrations: Assessment of available data for global application. Clin Chem 2008;54:559-66.
Kavaz A, Ozçakar ZB, Kendirli T, et al. Acute kidney injury in a paediatric intensive care unit: Comparison of the pRIFLE and AKIN criteria. Acta Paediatr 2012;101:e126-9.
Cao Y, Yi ZW, Zhang H, et al. Etiology and outcomes of acute kidney injury in Chinese children: A prospective multicentre investigation. BMC Urol 2013;13:41.
Imani PD, Odiit A, Hingorani SR, Weiss NS, Eddy AA. Acute kidney injury and its association with in-hospital mortality among children with acute infections. Pediatr Nephrol 2013;28:2199-206.
Palmieri T, Lavrentieva A, Greenhalgh D. An assessment of acute kidney injury with modified RIFLE criteria in paediatric patients with severe burns. Intensive Care Med 2009;35:2125-9.
Basu RK, Prasad DP, Wong H, Wheeler DS. An update and review of acute kidney injury in paediatrics. Paediatr Crit Care Med 2011;12:339-47.
Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstien SL. Modified RIFLE criteria in critically ill children with acute kidney inury. Kidney Int 2007;71:1028-35.
Naik S, Sharma J, Yengkom R, Kalrao V, Mulay A. Acute kidney injury in critically ill children: Risk factors and outcomes. Indian J Crit Care Med 2014;18:129-33.
] [Full text]
Dr. Kamran Afzal
Division of Nephrology, Department of Pediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]